1. Anaphylactic histamine release from rat peritoneal mast cells is dependent on the presence of calcium ions. Graded increase of histamine release occurs as the calcium ion concentration is raised from 0.1 to 1.0 m-mole/l.2. Magnesium antagonizes the effect of calcium. The dissociation constant of the Mg-receptor complex was found to be 9.4 m-mole/l.3. Strontium will replace calcium ions in the activation of anaphylactic histamine release. Graded increase of histamine release occurs when the strontium ion concentration is raised from 1.0 to 10.0 m-mole/l.4. Magnesium also antagonizes the effect of strontium. The dissociation constant of the magnesium-receptor complex was found to be 11.0 m-mole/l.5. The log concentration-effect curve for strontium has a greater maximum and steeper slope than the curve for calcium.6. Measurements of the interaction of calcium and strontium ions are in agreement with the hypothesis that strontium possesses a higher efficacy but a lower affinity than calcium, for the ;calcium receptor' in mast cells.7. Barium will replace calcium in the activation of anaphylactic histamine release.